We will study variants of the Hepa 1clc7 mouse hepatoma cell line which have markedly increased or decreased ability to metabolize the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene. We will characterize these variants with respect to their content of certain microsomal drug-metabolizing enzyme activities, their content of cytosolic Ah receptor, and their karyotype. We will use the fluorescence-activated cell sorter to assess heterogeneity in benzo(a)pyrene metabolism among the variants. We will construct molecules containing the DNA sequence for aromatic hydrocarbon-induced cytochrome P450 and DNA sequence for the cytosolic receptor, and we will use these probes to study the structure and function of these genes in the variants. These studies will increase our understanding of the control of carcinogen-metabolizing enzymes and the role which the Ah receptor plays in governing the activities of microsomal enzyme systems. They are relevant to health problems related to interindividual differences in drug metabolism and drug toxicity, drug interaction, and environmental carcinogenesis.